tbuckley/cabot-search huggingface dataset:
Superior Effectiveness of Tofacitinib Compared to Vedolizumab in Anti-TNF-experienced Ulcerative Colitis Patients: A Nationwide Dutch Registry Study
Authors: Tessa Straatmijer, Vince B.C. Biemans, Marijn Visschedijk, Frank Hoentjen, Annemarie de Vries, Adriaan A. van Bodegraven, Alexander Bodelier, Nanne K.H. de Boer, Gerard Dijkstra, Noortje Festen, Carmen Horjus, Jeroen M. Jansen, Bindia Jharap, Wout Mares, Fiona D.M. van Schaik, Cyriel Ponsioen, Tessa Romkens, Nidhi Srivastava, Michael M.P. J.A. van der Voorn, Rachel West, Janneke van der Woude, Marije D.J. Wolvers, Marieke Pierik, Andrea E. van der Meulen-de Jong, Marjolijn Duijvestein, Malena Schlotter, Martine van Workum, Dirk de Jong, Willemijn van Dop, S. van der Marel, Hayat El Ghabzouri, Kamila Talhaoui, Bas Oldenburg, Nynke Boontje, Herma Fidder, Meike Hirdes, Rob H. Creemers, J. Hoekstra, Jael Smid, Zlatan Mujagic, Marthe François-Verweij, Toos Schakel- van den Berge, Jeroen Maljaars, Rosaline Theeuwen, Denise van den Berg, Suzanne Gerretsen, Xenia Yocarini, Geert D’Haens, Mark Lowenberg, Joep Grootjans, Krisztina Gecse, Gerd Bouma, Petra Waaijenberg, Bart Muskens
Journal: Clinical Gastroenterology and Hepatology (2022)

Clinicians face difficulty in when and in what order to position biologics and Janus kinase inhibitors in patients with anti-tumor necrosis factor-alpha (TNF) refractory ulcerative colitis (UC). We aimed to compare the effectiveness and safety of vedolizumab and tofacitinib in anti-TNF-exposed patients with UC in our prospective nationwide Initiative on Crohn and Colitis Registry.Patients with UC who failed anti-TNF treatment and initiated vedolizumab or tofacitinib treatment were identified in the Initiative on Crohn and Colitis Registry in the Netherlands. We selected patients with both clinical as well as biochemical or endoscopic disease activity at initiation of therapy. Patients previously treated with vedolizumab or tofacitinib were excluded. Corticosteroid-free clinical remission (Simple Clinical Colitis Activity Index ≤2), biochemical remission (C-reactive protein ≤5 mg/L or fecal calprotectin ≤250 μg/g), and safety outcomes were compared after 52 weeks of treatment. Inverse propensity score-weighted comparison was used to adjust for confounding and selection bias.Overall, 83 vedolizumab- and 65 tofacitinib-treated patients were included. Propensity score-weighted analysis showed that tofacitinib-treated patients were more likely to achieve corticosteroid-free clinical remission and biochemical remission at weeks 12, 24, and 52 compared with vedolizumab-treated patients (odds ratio [OR], 6.33; 95% confidence interval [CI], 3.81-10.50; P < .01; OR, 3.02; 95% CI, 1.89-4.84; P < .01; and OR, 1.86; 95% CI, 1.15-2.99; P = .01; and OR, 3.27; 95% CI, 1.96-5.45; P < .01; OR, 1.87; 95% CI, 1.14-3.07; P = .01; and OR, 1.81; 95% CI, 1.06-3.09; P = .03, respectively). There was no difference in infection rate or severe adverse events.Tofacitinib was associated with superior effectiveness outcomes compared with vedolizumab in anti-TNF-experienced patients with UC along with comparable safety outcomes.
Sleep deprivation as a treatment for major depressive episodes: A systematic review and meta-analysis
Authors: Pamina Mitter, Franco De Crescenzo, Kimberley Loo Yong Kee, Jun Xia, Samantha Roberts, Wenjie Chi, Ayse Kurtulmus, Simon D. Kyle, John R. Geddes, Andrea Cipriani
Journal: Sleep Medicine Reviews (2022)

Sleep deprivation, alone or in combination with pharmacological treatment and as part of a chronotherapy package, is of potential use for people with major depressive episodes, however the evidence base is still conflicting. The aim of this systematic review and meta-analysis is to assess the clinical effects of sleep deprivation in comparison to any other intervention for the acute and long-term treatment of mood disorders. We searched electronic databases and trial registries (last update: 16th October 2021) for published and unpublished randomised controlled trials recruiting participants with a major depressive episode in unipolar or bipolar affective disorder. The clinical outcomes of interest were the reduction in depressive symptoms at different timepoints and the number of participants experiencing at least one side effect. Overall, 29 trials (1246 participants) were included. We did not find any difference in change in symptoms or all-cause discontinuation between interventions including SD compared to a control of the same intervention except without SD. In the included studies there were no available data for adverse events. Using the most methodologically rigorous approach, we did not find evidence that the addition of sleep deprivation to treatment packages leads to enhanced depressive outcomes.
Spatial and Transcriptomic Analysis of Perineural Invasion in Oral Cancer
Authors: Ligia B. Schmitd, Cindy Perez-Pacheco, Emily L. Bellile, Weisheng Wu, Keith Casper, Michelle Mierzwa, Laura S. Rozek, Gregory T. Wolf, Jeremy M.G. Taylor, Nisha J. D'Silva
Journal: Clinical Cancer Research (2022)

Perineural invasion (PNI), a common occurrence in oral squamous cell carcinomas, is associated with poor survival. Consequently, these tumors are treated aggressively. However, diagnostic criteria of PNI vary and its role as an independent predictor of prognosis has not been established. To address these knowledge gaps, we investigated spatial and transcriptomic profiles of PNI-positive and PNI-negative nerves.Tissue sections from 142 patients were stained with S100 and cytokeratin antibodies. Nerves were identified in two distinct areas: tumor bulk and margin. Nerve diameter and nerve-to-tumor distance were assessed; survival analyses were performed. Spatial transcriptomic analysis of nerves at varying distances from tumor was performed with NanoString GeoMx Digital Spatial Profiler Transcriptomic Atlas.PNI is an independent predictor of poor prognosis among patients with metastasis-free lymph nodes. Patients with close nerve-tumor distance have poor outcomes even if diagnosed as PNI negative using current criteria. Patients with large nerve(s) in the tumor bulk survive poorly, suggesting that even PNI-negative nerves facilitate tumor progression. Diagnostic criteria were supported by spatial transcriptomic analyses of >18,000 genes; nerves in proximity to cancer exhibit stress and growth response changes that diminish with increasing nerve-tumor distance. These findings were validated in vitro and in human tissue.This is the first study in human cancer with high-throughput gene expression analysis in nerves with striking correlations between transcriptomic profile and clinical outcomes. Our work illuminates nerve-cancer interactions suggesting that cancer-induced injury modulates neuritogenesis, and supports reclassification of PNI based on nerve-tumor distance rather than current subjective criteria.
Cellulose-based composite scaffolds for bone tissue engineering and localized drug delivery
Authors: Mahsa Janmohammadi, Zahra Nazemi, Amin Orash Mahmoud Salehi, Amir Seyfoori, Johnson V. John, Mohammad Sadegh Nourbakhsh, Mohsen Akbari
Journal: Bioactive Materials (2022)

Natural bone constitutes a complex and organized structure of organic and inorganic components with limited ability to regenerate and restore injured tissues, especially in large bone defects. To improve the reconstruction of the damaged bones, tissue engineering has been introduced as a promising alternative approach to the conventional therapeutic methods including surgical interventions using allograft and autograft implants. Bioengineered composite scaffolds consisting of multifunctional biomaterials in combination with the cells and bioactive therapeutic agents have great promise for bone repair and regeneration. Cellulose and its derivatives are renewable and biodegradable natural polymers that have shown promising potential in bone tissue engineering applications. Cellulose-based scaffolds possess numerous advantages attributed to their excellent properties of non-toxicity, biocompatibility, biodegradability, availability through renewable resources, and the low cost of preparation and processing. Furthermore, cellulose and its derivatives have been extensively used for delivering growth factors and antibiotics directly to the site of the impaired bone tissue to promote tissue repair. This review focuses on the various classifications of cellulose-based composite scaffolds utilized in localized bone drug delivery systems and bone regeneration, including cellulose-organic composites, cellulose-inorganic composites, cellulose-organic/inorganic composites. We will also highlight the physicochemical, mechanical, and biological properties of the different cellulose-based scaffolds for bone tissue engineering applications.
dbDEMC 3.0: Functional Exploration of Differentially Expressed miRNAs in Cancers of Human and Model Organisms
Authors: Feng Xu, Yifan Wang, Yunchao Ling, Chenfen Zhou, Haizhou Wang, Andrew E. Teschendorff, Yi Zhao, Haitao Zhao, Yungang He, Guoqing Zhang, Zhen Yang
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract M icroRNAs (miRNAs) are important regulators in gene expression. The dysregulation of miRNA expression is widely reported in the transformation from physiological to pathological states of cells. A large number of differentially expressed miRNAs (DEMs) have been identified in various human cancers by using high-throughput technologies, such as microarray and miRNA-seq. Through mining of published studies with high-throughput experiment information, the database of DEMs in human cancers (dbDEMC) was constructed with the aim of providing a systematic resource for the storage and query of the DEMs. Here we report an update of the dbDEMC to version 3.0, which contains two-fold more data entries than the second version and now includes also data from mice and rats. The dbDEMC 3.0 contains 3268 unique DEMs in 40 different cancer types. The current datasets for differential expression analysis have expanded to 9 generalized categories. Moreover, the current release integrates functional annotations of DEMs obtained by using experimentally validated targets. The annotations can be of great benefit to the intensive analysis of the roles of DEMs in cancer. In summary, dbDEMC 3.0 provides a valuable resource for characterizing molecular functions and regulatory mechanisms of DEMs in human cancers. The dbDEMC 3.0 is freely accessible at https://www.biosino.org/dbDEMC.
Screening of organoids derived from patients with breast cancer implicates the repressor NCOR2 in cytotoxic stress response and antitumor immunity
Authors: Kelvin K. Tsai, Shenq-Shyang Huang, Jason J. Northey, Wen-Ying Liao, Chung-Chi Hsu, Li-Hsin Cheng, Michael E. Werner, Chih-Pin Chuu, Chandrima Chatterjee, Jonathon N. Lakins, Valerie M. Weaver
Journal: Nature Cancer (2022)
Effect of novel antimalarial ZY-19489 on Plasmodium falciparum viability in a volunteer infection study
Authors: Georges F R Radohery, Jeremy Gower, Bridget E Barber, Kevinkumar Kansagra, Jörg J Möhrle, Miles P Davenport, James S McCarthy, David S Khoury, Maria Rebelo
Journal: The Lancet Infectious Diseases (2022)
Effect of Supine vs Prone Breast Radiotherapy on Acute Toxic Effects of the Skin Among Women With Large Breast Size
Authors: Danny Vesprini, Melanie Davidson, Sandi Bosnic, Pauline Truong, Isabelle Vallieres, Louis Fenkell, Daria Comsa, Medhat El-Mallah, Lourdes Garcia, Christiaan Stevens, Keith Nakonechny, William Tran, Alex Kiss, Eileen Rakovitch, Jean-Phillippe Pignol
Journal: JAMA Oncology (2022)

<h3>Importance</h3> Women with large breast size treated with adjuvant breast radiotherapy (RT) have a high rate of acute toxic effects of the skin. Breast RT in the prone position is one strategy that may decrease these toxic effects. <h3>Objective</h3> To determine if breast RT in the prone position reduces acute toxic effects of the skin when compared with treatment in the supine position. <h3>Design, Setting, and Participants</h3> This phase 3, multicenter, single-blind randomized clinical trial accrued patients from 5 centers across Canada from April 2013 to March 2018 to compare acute toxic effects of breast RT for women with large breast size (bra band ≥40 in and/or ≥D cup) in the prone vs supine positions. A total of 378 patients were referred for adjuvant RT and underwent randomization. Seven patients randomized to supine position were excluded (5 declined treatment and 2 withdrew consent), and 14 patients randomized to prone position were excluded (4 declined treatment, 3 had unacceptable cardiac dose, and 7 were unable to tolerate being prone). Data were analyzed from April 2019 through September 2020. <h3>Interventions</h3> Patients were randomized to RT in the supine or prone position. From April 2013 until June 2016, all patients (n = 167) received 50 Gy in 25 fractions (extended fractionation) with or without boost (range, 10-16 Gy). After trial amendment in June 2016, the majority of patients (177 of 190 [93.2%]) received the hypofractionation regimen of 42.5 Gy in 16 fractions. <h3>Main Outcomes and Measures</h3> Main outcome was moist desquamation (desquamation). <h3>Results</h3> Of the 357 women (mean [SD] age, 61 [9.9] years) included in the analysis, 182 (51.0%) were treated in the supine position and 175 (49.0%) in prone. There was statistically significantly more desquamation in patients treated in the supine position compared with prone (72 of 182 [39.6%] patients vs 47 of 175 [26.9%] patients; OR, 1.78; 95% CI, 1.24-2.56;<i>P</i> = .002), which was confirmed on multivariable analysis (OR, 1.99; 95% CI, 1.48-2.66;<i>P</i> &lt; .001), along with other independent factors: use of boost (OR, 2.71; 95% CI, 1.95-3.77;<i>P</i> &lt; .001), extended fractionation (OR, 2.85; 95% CI, 1.41-5.79;<i>P</i> = .004), and bra size (OR, 2.56; 95% CI, 1.50-4.37;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> This randomized clinical trial confirms that treatment in the prone position decreases desquamation in women with large breast size receiving adjuvant RT. It also shows increased toxic effects using an RT boost and conventional fractionation. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01815476
SARS-CoV-2 Attack Rate and Population Immunity in Southern New England, March 2020 to May 2021
Authors: Thu Nguyen-Anh Tran, Nathan B. Wikle, Fuhan Yang, Haider Inam, Scott Leighow, Bethany Gentilesco, Philip Chan, Emmy Albert, Emily R. Strong, Justin R. Pritchard, William P. Hanage, Ephraim M. Hanks, Forrest W. Crawford, Maciej F. Boni
Journal: JAMA Network Open (2022)

In emergency epidemic and pandemic settings, public health agencies need to be able to measure the population-level attack rate, defined as the total percentage of the population infected thus far. During vaccination campaigns in such settings, public health agencies need to be able to assess how much the vaccination campaign is contributing to population immunity; specifically, the proportion of vaccines being administered to individuals who are already seropositive must be estimated. To estimate population-level immunity to SARS-CoV-2 through May 31, 2021, in Rhode Island, Massachusetts, and Connecticut. This observational case series assessed cases, hospitalizations, intensive care unit occupancy, ventilator occupancy, and deaths from March 1, 2020, to May 31, 2021, in Rhode Island, Massachusetts, and Connecticut. Data were analyzed from July 2021 to November 2021. COVID-19-positive test result reported to state department of health. The main outcomes were statistical estimates, from a bayesian inference framework, of the percentage of individuals as of May 31, 2021, who were (1) previously infected and vaccinated, (2) previously uninfected and vaccinated, and (3) previously infected but not vaccinated. At the state level, there were a total of 1 160 435 confirmed COVID-19 cases in Rhode Island, Massachusetts, and Connecticut. The median age among individuals with confirmed COVID-19 was 38 years. In autumn 2020, SARS-CoV-2 population immunity (equal to the attack rate at that point) in these states was less than 15%, setting the stage for a large epidemic wave during winter 2020 to 2021. Population immunity estimates for May 31, 2021, were 73.4% (95% credible interval [CrI], 72.9%-74.1%) for Rhode Island, 64.1% (95% CrI, 64.0%-64.4%) for Connecticut, and 66.3% (95% CrI, 65.9%-66.9%) for Massachusetts, indicating that more than 33% of residents in these states were fully susceptible to infection when the Delta variant began spreading in July 2021. Despite high vaccine coverage in these states, population immunity in summer 2021 was lower than planned owing to an estimated 34.1% (95% CrI, 32.9%-35.2%) of vaccines in Rhode Island, 24.6% (95% CrI, 24.3%-25.1%) of vaccines in Connecticut, and 27.6% (95% CrI, 26.8%-28.6%) of vaccines in Massachusetts being distributed to individuals who were already seropositive. These findings suggest that future emergency-setting vaccination planning may have to prioritize high vaccine coverage over optimized vaccine distribution to ensure that sufficient levels of population immunity are reached during the course of an ongoing epidemic or pandemic.
The bone marrow niche regulates redox and energy balance in MLL::AF9 leukemia stem cells
Authors: Ana C. Viñado, Isabel A. Calvo, Itziar Cenzano, Danel Olaverri, Miguel Cocera, Patxi San Martin-Uriz, Juan P. Romero, Amaia Vilas-Zornoza, Laura Vera, Nuria Gomez-Cebrian, Leonor Puchades-Carrasco, Livia E. Lisi-Vega, Iñigo Apaolaza, Pablo Valera, Elisabeth Guruceaga, Froilan Granero-Molto, Purificacion Ripalda-Cemborain, Tamara J. Luck, Lars Bullinger, Francisco J. Planes, José J. Rifon, Simón Méndez-Ferrer, Rushdia Z. Yusuf, Ana Pardo-Saganta, Felipe Prosper, Borja Saez
Journal: Leukemia (2022)
Historical Redlining Impacts Contemporary Environmental and Asthma-related Outcomes in Black Adults
Authors: Alexander J. Schuyler, Sally E. Wenzel
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Environmental threats and poorly controlled asthma disproportionately burden Black people. Some have attributed this to socioeconomic or biologic factors; however, racism, specifically historical redlining, a U.S. discriminatory mortgage lending practice in existence between the 1930s and the 1970s, may have actuated and then perpetuated poor asthma-related outcomes.
Wastewater-Based Estimation of the Effective Reproductive Number of SARS-CoV-2
Authors: Jana S. Huisman, Jérémie Scire, Lea Caduff, Xavier Fernandez-Cassi, Pravin Ganesanandamoorthy, Anina Kull, Andreas Scheidegger, Elyse Stachler, Alexandria B. Boehm, Bridgette Hughes, Alisha Knudson, Aaron Topol, Krista R. Wigginton, Marlene K. Wolfe, Tamar Kohn, Christoph Ort, Tanja Stadler, Timothy R. Julian
Journal: Environmental Health Perspectives (2022)

Background: The effective reproductive number, Re, is a critical indicator to monitor disease dynamics, inform regional and national policies, and estimate the effectiveness of interventions. It describes the average number of new infections caused by a single infectious person through time. To date, Re estimates are based on clinical data such as observed cases, hospitalizations, and/or deaths. These estimates are temporarily biased when clinical testing or reporting strategies change. Objectives: We show that the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in wastewater can be used to estimate Re in near real time, independent of clinical data and without the associated biases. Methods: We collected longitudinal measurements of SARS-CoV-2 RNA in wastewater in Zurich, Switzerland, and San Jose, California, USA. We combined this data with information on the temporal dynamics of shedding (the shedding load distribution) to estimate a time series proportional to the daily COVID-19 infection incidence. We estimated a wastewater-based Re from this incidence. Results: The method to estimate Re from wastewater worked robustly on data from two different countries and two wastewater matrices. The resulting estimates were as similar to the Re estimates from case report data as Re estimates based on observed cases, hospitalizations, and deaths are among each other. We further provide details on the effect of sampling frequency and the shedding load distribution on the ability to infer Re. Discussion: To our knowledge, this is the first time Re has been estimated from wastewater. This method provides a low-cost, rapid, and independent way to inform SARS-CoV-2 monitoring during the ongoing pandemic and is applicable to future wastewater-based epidemiology targeting other pathogens. https://doi.org/10.1289/EHP10050
Host hepatic metabolism is modulated by gut microbiota-derived sphingolipids
Authors: Henry H. Le, Min-Ting Lee, Kevin R. Besler, Elizabeth L. Johnson
Journal: Cell Host & Microbe (2022)

Microbially-derived gut metabolites are important contributors to host phenotypes, many of which may link microbiome composition to metabolic disease. However, relatively few metabolites with known bioactivity have been traced from specific microbes to host tissues. Here, we use a labeling strategy to characterize and trace bacterial sphingolipids from the gut symbiont Bacteroides thetaiotaomicron to mouse colons and livers. We find that bacterial sphingolipid synthesis rescues excess lipid accumulation in a mouse model of hepatic steatosis and observe the transit of a previously uncharacterized bacterial sphingolipid to the liver. The addition of this sphingolipid to hepatocytes improves respiration in response to fatty-acid overload, suggesting that sphingolipid transfer to the liver could potentially contribute to microbiota-mediated liver function. This work establishes a role for bacterial sphingolipids in modulating hepatic phenotypes and defines a workflow that permits the characterization of other microbial metabolites with undefined functions in host health.
Immune disease risk variants regulate gene expression dynamics during CD4+ T cell activation
Authors: Blagoje Soskic, Eddie Cano-Gamez, Deborah J. Smyth, Kirsty Ambridge, Ziying Ke, Julie C. Matte, Lara Bossini-Castillo, Joanna Kaplanis, Lucia Ramirez-Navarro, Anna Lorenc, Nikolina Nakic, Jorge Esparza-Gordillo, Wendy Rowan, David Wille, David F. Tough, Paola G. Bronson, Gosia Trynka
Journal: Nature Genetics (2022)

Abstract During activation, T cells undergo extensive gene expression changes that shape the properties of cells to exert their effector function. Understanding the regulation of this process could help explain how genetic variants predispose to immune diseases. Here, we mapped genetic effects on gene expression (expression quantitative trait loci (eQTLs)) using single-cell transcriptomics. We profiled 655,349 CD4 + T cells, capturing transcriptional states of unstimulated cells and three time points of cell activation in 119 healthy individuals. This identified 38 cell clusters, including transient clusters that were only present at individual time points of activation. We found 6,407 genes whose expression was correlated with genetic variation, of which 2,265 (35%) were dynamically regulated during activation. Furthermore, 127 genes were regulated by variants associated with immune-mediated diseases, with significant enrichment for dynamic effects. Our results emphasize the importance of studying context-specific gene expression regulation and provide insights into the mechanisms underlying genetic susceptibility to immune-mediated diseases.